The selective reduction of heterocyclic rings in benzo-fused nitrogen compounds such as quinoxalines is an important reaction in organic synthesis since the corresponding tetrahydro products serve as key intermediates in the preparation of drugs, agrochemicals, dyes, higher alkaloids etc. Numerous synthetic methods have been utilized for this desired transformation; however, conventional procedures often require extended reaction times, substantial purifications, and result in mixtures of stereoisomers. Therefore, we wish to report a rapid, easy, and efficient method for the selective reduction of various substituted quinoxalines. Mono- and di-substituted alkyl and aryl quinoxalines were rapidly reduced in high yield to afford their respective 1, 2, 3, 4-tetrahydro derivatives by in-situ generated borane in THF solution. Solutions of borane-THF were smoothly generated from the reaction of iodomethane with lithium borohydride in anhydrous THF. In the case of the 2, 3-di-substituted compounds, reduction was stereoselective, yielding exclusively the corresponding cis-isomers. Therefore, high yields and fast reaction times render the LiBH4-CH3I in THF system a superior reagent for the transformation of quinoxalines to 1, 2, 3, 4-tetrahydroquinoxalines. Currently, we are extending this protocol toward the reduction of various other nitrogen heterocycles and application of this procedure toward the reduction of quinoxaline macrocycles and quinoxaline cavitands, respectively.

Rapid and efficient method for the reduction of quinoxalines using LiBH4 and CH3I: Synthesis of 1, 2, 3, 4-tetrahydroquinoxalines

2019 Spring National Meeting

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